Effects of Th2 cytokines and eosinophils on stem cell factor production by lung fibroblasts

Abstract

ABSTRACT Background Although eosinophils and fibroblasts are believed to play important roles in the pathogenesis of chronic allergic inflammation, the interaction between eosinophils and fibroblasts has not been thoroughly elucidated. Stem cell factor (SCF) is one of the important cytokines produced by fibroblasts. In the present study, we examined the effects of some cytokines and eosinophils on SCF production by human lung fibroblasts. Methods Fibroblasts were cultured with or without interleukin (IL)-4 for up to 48 h. In some experiments, eosinophils were added to the wells after incubation with or without IL-5 for 3 h and cells were cultured for up to 48 h. At the end of the culture period, SCF in the supernatants was measured by ELISA. In addition, the expression of SCF mRNA was examined using reverse transcription-polymerase chain reaction analysis. Results Interleukin-4 significantly enhanced SCF production, whereas tumor necrosis factor-α, interferon-γ and IL-1α showed suppressive effects on SCF production. When fibroblasts were cultured with IL-4 plus IL-5-activated eosinophils, SCF production was significantly enhanced in comparison with IL-4 alone. Experiments using polymerase chain reaction amplification revealed that IL-5-activated eosinophils enhanced SCF production by fibroblasts through transcriptional gene activation. Conclusions These results suggest that some factor from activated eosinophils may interact in a synergistic fashion with IL-4 to further augment SCF production by fibroblasts and that eosinophils may play an important role in the activation of fibroblasts in chronic allergic inflammation.